Glycan-dependent HIV-specific neutralizing antibodies bind to cells of uninfected individuals
Glycan-dependent HIV-specific neutralizing antibodies bind to cells of uninfected individuals
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DOI：
10.1172/jci125955
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发表时间：
2019-11-01
影响因子：
15.9
通讯作者：
Chun, Tae-Wook
中科院分区：
文献类型：
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作者：
Blazkova, Jana;Refsland, Eric W.;Chun, Tae-Wook
最近，一些针对人类免疫缺陷病毒(HIV)的高效和广谱中和抗体(BNAbs)被证明可以防止病毒的传播，抑制病毒复制，并在动物模型和受感染的人类中停止抗逆转录病毒治疗后延迟血浆病毒反弹。然而，这种bNAb与初级淋巴细胞相互作用的程度和程度尚未完全描述。在这里，我们发现某些依赖糖的bNAbs，如PGT121和PGT151，与HIV感染者和非感染者的B细胞、活化T细胞和自然杀伤(NK)细胞结合。这些bNAb，特别是PGT121和PGT151，与活化的CD4(+)和CD8(+)T细胞的结合是由复合型多糖介导的，并通过酶抑制N-连接的糖基化而被取消。此外，短期孵育PGT151和原代NK细胞会导致脱颗粒和细胞死亡。我们的数据表明，某些bNAbs与未感染/旁观者细胞结合的倾向在被动转移研究中有可能出现意想不到的结果，并强调了针对初级淋巴细胞的抗体筛选的重要性。
A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans. However, the degree and extent to which such bNAbs interact with primary lymphocytes have not been fully delineated. Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals. Binding of these bNAbs, particularly PGT121 and PGT151, to activated CD4(+) and CD8(+) T cells was mediated by complex-type glycans and was abrogated by enzymatic inhibition of N-linked glycosylation. In addition, a short-term incubation of PGT151 and primary NK cells led to degranulation and cellular death. Our data suggest that the propensity of certain bNAbs to bind uninfected/bystander cells has the potential for unexpected outcomes in passive-transfer studies and underscore the importance of antibody screening against primary lymphocytes.